Multiple Causes of Pediatric Early Onset Chorea—Clinical and Genetic Approach

Lubov Blumkin; Tally Lerman-Sagie; Ana Westenberger; Hilla Ben-Pazi; Ayelet Zerem; Keren Yosovich; Dorit Lev

doi:10.1055/s-0038-1645884

Neuropediatrics, Table of Contents

Neuropediatrics 2018; 49(04): 246-255
DOI: 10.1055/s-0038-1645884

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Multiple Causes of Pediatric Early Onset Chorea—Clinical and Genetic Approach

Lubov Blumkin

¹Pediatric Movement Disorders Clinic, Wolfson Medical Center, Holon, Israel

²Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel

³Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel

⁴Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

,

Tally Lerman-Sagie

²Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel

³Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel

⁴Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

,

Ana Westenberger

⁵Institute of Neurogenetics, University of Lubeck, Lubeck, Germany

,

Hilla Ben-Pazi

⁶Pediatric Neurology Unit, Shaare Zedek Medical Center, Jerusalem, Israel

,

Ayelet Zerem

²Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel

³Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel

⁴Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

,

Keren Yosovich

³Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel

⁷Rina Mor Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel

⁸Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Israel

,

Dorit Lev

³Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel

⁴Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

⁷Rina Mor Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel

› Author Affiliations

Abstract

Objective This article elucidates a clinical and genetic approach to pediatric early-onset chorea in patients with normal neuroimaging.

Methods We retrospectively studied patients with onset hyperkinetic movement disorders. Only children with onset of chorea in the first 3 years of life were included, those with an abnormal magnetic resonance imaging (MRI) or electroencephalogram (EEG) were excluded.

We studied the movement disorder phenotype by clinical examination and by interpretation of videos and compared our data to the literature.

Results Four patients, aged 2 to 13 years, were diagnosed. Abnormal involuntary movements appeared between the ages of 6 months to 3 years in association with developmental delay. One patient has a close relative with NKX2.1-related chorea. One patient is from Iraqi-Jewish origin. Facial twitches and nocturnal dyskinetic attacks were observed in one.

The unique clinical presentation and family history enabled genetic diagnosis by molecular analysis of a specific mutation in two (NKX2.1, OPA3) and Sanger sequencing of a target gene in one (ADCY5). One patient was diagnosed by whole-exome sequencing (WES) (GNAO1).

Conclusion By carefully recording the phenotype and genetic background, a single gene can be suspected in some cases. In the rest, we suggest multigene panels or WES study.

Keywords

pediatric chorea - NKX2.1 - OPA3 - ADCY5 - GNAO1

Full Text

References

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